Traditional inotropic agents, e.g., those that increase myocardial contraction through enhanced cyclic AMP or those that increase contractility at a relatively high 02 cost are frequently not useful in the clinical setting. Accordingly, newer agents that operate through different mechanisms have been synthesized. The goal of the present study was to compare the effects of a new Ca2+ promotor, BAY y 5959, with more traditional inotropic agents, dobutamine and milrinone, in 11 conscious dogs chronically instrumented for measurement of left ventricular (LV) and arterial pressures, LV internal diameter, wall thickness, coronary blood flow, and arterial and coronary sinus 02 content. Equi-inotropic doses of BAY y 5959 (20 g.kg-1.min-1), dobutamine (10 g.kg-1.min-1), and milrinone (10 g.kg-1.min1) were selected, which increased the LV rate of pressure development in sinus rhythm by 71-78% from similar baselines. Heart rate rose with dobutamine (+24 q 4%) and milrinone (+23 q 2%) but fell with BAY y 5959 (-35 q 3%). Dobutamine increased myocardial O2 consumption (MV02) by 88 q 10%. In contrast, MV02 increased less with BAY y 5959 (+9 q 3%) and milrinone (+16 q 5%; P < 0.05). Furthermore, mechanical efficiency was also calculated either with direct measurement of cardiac output or by pressure-volume loops. Dobutamine and milrinone did not change efficiency; however, BAY y 5959 increased efficiency by 19 q 5%. With the heart rate held constant, BAY y 5959 increased MVO2 by 32 q 4% but still increased efficiency by 28 q 7%. Thus the Ca2+ promotor BAY y 5959 has unique features that might be desirable for clinical applications where inotropic support is indicated, but increased MVO2 without enhanced mechanical efficiency is deleterious.